PBT assessment under REACH: Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish
| Autor: | Sebastian Strempel, Ralph Kühne, Anna Lombardo, Gerrit Schüürmann, Monika Nendza |
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| Rok vydání: | 2018 |
| Předmět: |
Quantitative structure–activity relationship
Food Chain Environmental Engineering Quantitative Structure-Activity Relationship Bioconcentration 010501 environmental sciences Ecotoxicology Risk Assessment 01 natural sciences In vivo Animals Environmental Chemistry Waste Management and Disposal 0105 earth and related environmental sciences Alternative methods Training set Chemistry Fishes Pollution 0104 chemical sciences 010404 medicinal & biomolecular chemistry Bioaccumulation Environmental chemistry Fish Hydrophobic and Hydrophilic Interactions Water Pollutants Chemical Environmental Monitoring Applicability domain |
| Zdroj: | Science of The Total Environment. :97-106 |
| ISSN: | 0048-9697 |
| DOI: | 10.1016/j.scitotenv.2017.10.317 |
| Popis: | Aquatic bioconcentration factors (BCFs) are critical in PBT (persistent, bioaccumulative, toxic) and risk assessment of chemicals. High costs and use of more than 100 fish per standard BCF study (OECD 305) call for alternative methods to replace as much in vivo testing as possible. The BCF waiving scheme is a screening tool combining QSAR classifications based on physicochemical properties related to the distribution (hydrophobicity, ionisation), persistence (biodegradability, hydrolysis), solubility and volatility (Henry's law constant) of substances in water bodies and aquatic biota to predict substances with low aquatic bioaccumulation (nonB, BCF The BCF waiving scheme was developed with a dataset of reliable BCFs for 998 compounds and externally validated with another 181 substances. It performs with 100% sensitivity (no false negatives), > 50% efficacy (waiving potential), and complies with the OECD principles for valid QSARs. The chemical applicability domain of the BCF waiving scheme is given by the structures of the training set, with some compound classes explicitly excluded like organometallics, poly- and perfluorinated compounds, aromatic triphenylphosphates, surfactants. The prediction confidence of the BCF waiving scheme is based on applicability domain compliance, consensus modelling, and the structural similarity with known nonB and B/vB substances. Compounds classified as nonB by the BCF waiving scheme are candidates for waiving of BCF in vivo testing on fish due to low concern with regard to the B criterion. The BCF waiving scheme supports the 3Rs with a possible reduction of > 50% of BCF in vivo testing on fish. If the target chemical is outside the applicability domain of the BCF waiving scheme or not classified as nonB, further assessments with in silico, in vitro or in vivo methods are necessary to either confirm or reject bioaccumulative behaviour. |
| Databáze: | OpenAIRE |
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